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Research Article

Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy

  • Jingqiu Chen equal contributor,

    equal contributor Contributed equally to this work with: Jingqiu Chen, Daniel Korostyshevsky

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

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  • Daniel Korostyshevsky equal contributor,

    equal contributor Contributed equally to this work with: Jingqiu Chen, Daniel Korostyshevsky

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

    X
  • Sean Lee,

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

    X
  • Ethan O. Perlstein mail

    eperlste@princeton.edu

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

    X
  • Published: April 18, 2012
  • DOI: 10.1371/journal.pone.0034024

Reader Comments (16)

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Genetics of psychoactive medications

Posted by ebuttner on 08 Jun 2012 at 20:12 GMT

This interesting paper underscores the utility of simple genetic organisms in analyzing the mechanims of action of psychoactive medications. Supportive evidence for a SERT-independent mechanism of action for SSRIs comes in part from Jim Thomas' C. elegans lab. They showed that fluoxetine-resistant nrf mutants encode a novel family of transmembrane proteins. In the future, it would be interesting to see if the nrf genes play a role in the processes described by Chen et al.
- E Buttner, McLean Hospital

No competing interests declared.

RE: Genetics of psychoactive medications

eperlste replied to ebuttner on 14 Jun 2012 at 14:42 GMT

Thanks for the comment! I'm re-reading Thomas' 2006 Genetics paper now. nrf mutants are definitely modifying fluoxetine drug transport but I disagree with their proposed mechanism.

Consider the cellular response as a reaction to membrane accumulation. NRF genes may be mediating membrane adaptation to the 10 minute surge of 1mg/ml fluoxetine that is used to trigger nose contraction. Fluoxetine is, after all, a cationic amphipath. And SSRI experiments with worms use *really high* concentrations, so it seems unreasonable to ignore the physical effects of drug on cell membranes.

No competing interests declared.